The FDA advisory committee met and voted 11 to 2 against recommending approval of Brinavess, citing safety concerns. The FDA is not required to follow the recommendations of its adcoms, but typically does.
Correvio Pharma Corp., based in Vancouver, British Columbia, indicated that it is considering a sale after a U.S. Food and Drug Administration (FDA) advisory committee voted against approving its Brinavess (vernakalant hydrochloride, IV). This is an antiarrhythmia drug for the rapid conversion of recent onset atrial fibrillation (AF) to sinus rhythm in adults.
Brinavess is already approved for marketing in Europe, Canada and several other countries. It is approved in the EU for rapid conversion of recent onset atrial fibrillation to sinus rhythm in adults for non-surgery patients who had AF less than 7 days duration, for post-cardiac surgery patients with AF less than 3 days duration. It is not yet approved in the U.S.
Correvio has a target action date of December 24, 2019 for its resubmitted New Drug Application (NDA) for Brinavess. However, the FDA advisory committee met and voted 11 to 2 against recommending approval of Brinavess, citing safety concerns. The FDA is not required to follow the recommendations of its adcoms, but typically does.
The NDA was built on data from SPECTRUM, a post-authorization safety study conducted in Europe of 1,778 unique patients across a total of 2,009 treatment episodes after dosing of Brinavess. The data showed that Brinavess successfully converted 70.2% of the treated AF patients into normal sinus rhythm. It also demonstrated a median time to conversion of 11 minutes from the start of the first infusion in the patients who were successfully converted.
“Given yesterday’s FDA’s Cardiovascular and Renal Drugs Advisory Committee (CRDAC) meeting outcome for Brinavess (vernakalant IV) for the conversion of atrial fibrillation (AF), we believe it is in the best interest of our stakeholders to expand our internal corporate development efforts and formally evaluate strategic alternatives for the company,” said Mark H.N. Corrigan, Correvio’s chief executive officer.
Corrigan added, “We have a strong and growing commercial portfolio of assets being sold across the globe and we will immediately begin preparations for a potential strategic transaction while we await the U.S. Food and Drug Administration (FDA)’s decision regarding Brinavess. We are also taking steps to reduce operating costs outside the core European commercial business and a transaction committee has been formed within the Board of Directors.”
The adcom’s vote was an indication they did not believe the benefit-risk profile of the drug was enough to support approval.
The company’s commercial portfolio outside the U.S. is expected to bring in about $30 million in revenue this year. That portfolio is made up of four approved and commercialized branded products and one product candidate. They are Xydalba (dalbavancin hydrochloride) for acute bacterial skin and skin structure infections; Zevtera/Mabelio (ceftobiprole medocaril sodium), an antibiotic for community- and hospital-acquired pneumonia; Brinavess; Aggrastat (tirofiban hydrochloride) for the reduction of thrombotic cardiovascular events in patients with acute coronary syndrome; and Trevyent, a drive device combination that delivers treprostinil, a treatment for pulmonary arterial hypertension.
Correvio has hired Piper Jaffray to help review its strategic options. Without indicating whether it expected job cuts, the company stated it planned to reduce its operating costs in North America. This way it would focus its resources on essential commercial and business development activities.
Correvio has made attempts to get approval for Brinavess in the U.S. since 2006. The FDA has never approved it because of safety concerns. At one point the U.S. trials were placed on hold after the death of a patient. The clinical hold is still in place.
In a 2014 research and review paper in Current Cardiology Reviews, John Camm, with St. George’s University of London, UK, wrote, “The terms of the [European] approval are very strictly aligned to the evidence base for vernakalant. … Regulators were able to label the drug to avoid the majority of other adverse effects of vernakalant offered an alternative to amiodarone in patients with mild or moderate heart disease. Although amiodarone achieves conversion in a high proportion of patients its action is relatively delayed. A clear unmet need could potentially be filled by this new antiarrhythmic drug.”
Although the paper is five years old, Camm’s conclusion likely holds today: “The difference between regulatory opinions on both sides of the Atlantic is disturbing and perplexing. Agencies in Europe and the USA came to different conclusions when examining the same evidence-base. Thus, neither opinion can be entirely or easily accepted.”
